The two-hour special will be screened in the US on Sunday, and on Monday evening in Ireland and the UK
It has become one of the most talked about royal spectacles for decades.
Oprah Winfrey has promised shocking content with no subject off limits and even the Queen has not been given an advance copy.
As the world waits to see what the Duke and Duchess of Sussex will reveal in their televised two-hour tell-all primetime show, here is what to look out for and what questions need answering in the continuing soap opera saga of Harry and Meghan.
The crunch point of the interview will be whether the couple specifically mention or criticise the monarch or other members of the royal family.
The royal family will be waiting to see what the Sussexes say
Any fault-finding with one royal will be taken as an attack on the Windsors as a whole.
Harry is known to have a good relationship with his grandmother and is unlikely to want to disrespect her, but the royal family and their aides will be waiting to see how they come across when the Sussexes spill the beans about behind the scenes royal life.
Whether the Prince of Wales or even Harry’s stepmother the Duchess of Cornwall feature will also be crucial, particularly as the duke is set to refer to his late mother Diana, Princess of Wales.
Harry and William’s bond was once so close that any divide would have seemed unthinkable.
But their rift stretches back to before the wedding when Harry was angered by what he perceived as his brother’s “snobbish” attitude to Meghan, after William questioned whether he should rush into things with the ex-Suits star.
Kate has also faced accusations she did little to bridge the divide and never really got to know Meghan, and that she snubbed her at the Sussexes’ final public royal engagement on Commonwealth Day.
Any criticism of Kate would be expected to do irreparable damage to Harry’s relationship with William.